KR900018082A - Esters of phenylalkanoic acid - Google Patents

Abstract

The esters of phenylalkanoic acid of the formula: <CHEM> wherein R<1> is 4-10 membered, saturated or unsaturated, mono- or bi-cyclic hetero ring containing as hetero atoms: (i) one or two nitrogen, (ii) two or three of nitrogen and sulfur in total, or (iii) one or two sulfur; R<2> is hydrogen; or R<1> and R<2>, taken together with a nitrogen to which they are attached, form 4-7 membered, saturated or unsaturated, mono-cyclic hetero ring containing as hetero atoms: (i) one or two nitrogen, or (ii) two or three of nitrogen and oxygen in total, the aforementioned hetero rings, represented by R<1> or formed by R<1> and R<2>, taken together with a nitrogen to which they are attached, may be substituted by one substituent selected from C1-4 alkyl and C2-5 acyl; R<3> each, independently, is hydrogen or C1-4 alkyl; R<4> is hydrogen, halogen, trihalomethyl, C1-4 alkyl, C1-4 alkoxyl C2-5 acyl, cyano, nitro or nitroxy; R<5> each, independently, is hydrogen, C1-4 alkyl or phenyl; or the two R<5>'s, taken together with a carbon to which they are attached, form cyclopentane or cyclohexane; and the pharmaceutically acceptable acid addition salts thereof, have beta 1-adrenergic receptor blocking activity, and therefore, are useful for the prevention of and/or in the treatment of cardiovascular diseases such as angina pectoris, myocardial infarction, congestive heart failure, hypertension, arrhythmia, etc.

Description

Esters of phenylalkanoic acid

Since this is an open matter, no full text was included.

Claims (13)

Esters of phenylalkanoic acid of formula (I) and pharmaceutically acceptable acid addition salts thereof. Wherein R ¹ is a hetero atom (i) 4 to 10 membered containing 1 or 2 nitrogens, (ii) 2 or 3 nitrogen sulfurs in total, or (iii) 1 or 2 sulfurs, saturated or unsaturated, Mono or bicyclic hetero ring; R ² is hydrogen; and R ¹ and R ² together with the nitrogen to which they are attached are (i) one or two nitrogens, (ii) two or three in total as a hetero atom; 4- to 7-membered, saturated or unsaturated, mono-cyclic hetero rings comprising nitrogen and oxygen, wherein the hetero rings represented by R ¹ or R ¹ and R ² together with the nitrogen to which they are attached are C _1-4 alkyl And one substituent selected from C _2-5 acyl; and R ³ are each independently hydrogen or C _1-4 alkyl; R ⁴ is hydrogen, halogen, trihalomethyl, C _{1 -4} alkyl, C _1-4 alkoxy, C _2-5 acyl, cyano, nitro or nitrooxy; R | Each ⁵ is independently hydrogen, C _1-4 alkyl or phenyl; two R ⁵ together with the carbon to which they are attached form cyclopentane or cyclohexane. 2. A compound according to claim 1, wherein R ¹ and R ² together with the nitrogen to which they are attached form a 4 to 7 membered, saturated or unsaturated, mono-cyclic hetero ring containing a total of 2 or 3 nitrogens and oxygen as hetero atoms Ester. The ester of claim 1, wherein R ¹ and R ² together with the nitrogen to which they are attached represent a monopolyno group. The method of claim 3, wherein (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [4- [2-hydroxy-3- (2-morpholinocarbonylaminoethyl) amino Propoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [4- [2-hydroxy-3- (1,1-dimethyl-2- Morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (2-methyl-2-phenyl-1,3-dioxolan-4-yl) methyl 3- [4- [2-hydroxy- 3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (1,4-dioxaspiro [4,4] nonan-2-yl) methyl 3- [4- [2 -Hydroxy-3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [3 -Fluoro-4- [2-hydroxy-3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolane-4 -Yl) methyl 3- [3-methyl-4- [2-hydroxy-3- (2-morpholinocarbonylamino Methyl) aminopropoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [3-methoxy-4- [2-hydroxy-3- ( 2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolan-4-al) methyl 3- [3-acetyl-4- [2 -Hydroxy-3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate, (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [3 -Cyano-4- [2-hydroxy-3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate or (2,2-dimethyl-1,3-dioxolane-4 -Al) methyl 3- [3-nitro-4- [2-hydroxy-3- (2-morpholinocarbonylaminoethyl) aminopropoxy] phenyl] propionate. The ester of claim 1, wherein R ¹ and R ² together with the nitrogen to which they are attached form a 4 to 7 membered, saturated or unsaturated, mono-cyclic hetero ring containing 1 or 2 nitrogens. The ester of claim 1, wherein R ¹ and R ² together with the nitrogen to which they are attached represent piperazinyl. 7. A compound according to claim 6, wherein (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [4- [2-hydroxy-3- [2- (4-methylpiperazin-1- (I) carbonylaminoethyl) aminopropoxy] phenyl] propionate. The ester of claim 1, wherein R ¹ is a 4 to 10 membered, saturated or unsaturated, mono- or non-cyclic hetero ring containing 1 or 2 nitrogens as hetero atoms, and R ² is hydrogen. The ester of claim 1, wherein R ¹ is a pyridyl group and R ² is hydrogen. 10. The compound of claim 9, wherein (2,2-dimethyl-1,3-dioxolan-4-yl) methyl 3- [4- [2-hydroxy-3- [2- (4-pyridyl) amino carbonyl Aminoethyl) aminopropoxy] phenyl] propionate. (Iii) an ethoxide-cleaving reaction of a compound of formula (II) with a compound of formula (III), and (ii) an ester of phenyl alkanoic acid of formula (I), if necessary, with the corresponding acid A process for preparing esters of phenylalkanoic acid of formula (I) and pharmaceutically acceptable acid addition salts thereof, characterized by conversion to addition salts. Wherein R ¹ is a 4-10 membered, saturated or unsaturated, containing (i) one or two nitrogens, (ii) a total of two or three nitrogen sulfurs, or (iii) one or two sulfurs as a hetero atom Is a mono- or non-cyclic hetero ring; R ² is hydrogen; and R ¹ and R ² together with the nitrogen to which they are attached are (i) one or two nitrogens, or (ii) a total of two or 4- to 7-membered, saturated or unsaturated, mono-cyclic hetero rings containing three nitrogens and oxygen (herein represented as R ¹ or hetero rings formed by R ¹ and R ² together with the nitrogen to which they are attached are C _{1- 4} may be substituted with one substituent selected from alkyl and C _2-5 acyl; and R ³ is each independently hydrogen or C _1-4 alkyl; R ⁴ is hydrogen, halogen, trihalomethyl, C _1-4 alkyl, C _1-4 alkoxy, C _2-5 acyl, cyano, nitro or nitrooxy; R | Each ⁵ is independently hydrogen, C _1-4 alkyl or phenyl; two R ⁵ together with the carbon to which they are attached are cyclopentane or cyclohexane. A pharmaceutical composition comprising as an active ingredient an ester of phenylalkanoic acid of formula (I) according to claim 1 or a pharmaceutically acceptable acid addition salt thereof together with a pharmaceutical carrier or coating. An effective amount of an ester of phenylalkanoic acid of formula (I) according to claim 1 or a pharmaceutically acceptable acid addition salt thereof is administered, such as angina pectoris, cardiomyopathy, congestive heart failure, hypertension, and arrhythmia. How to prevent and treat cardiovascular diseases. ※ Note: The disclosure is based on the initial application.